Tourette Syndrome is a neuropsychiatric disorder, the hallmark of which is the presence of multiple, involuntary motor and vocal tics. The mode of inheritance of this disorder best fits an autosomal dominant pattern. Despite the large number of pedigrees with multiple affected members, no linkage with any genetic marker has been found. The lack of success with linkage analysis suggests that the genetic mechanism leading to the disorder may be more complex than originally anticipated. Thus, alternative approaches to identifying a gene involved with Tourette syndrome should be considered. A pedigree has been previously described where a 7;18 balanced translocation was inherited in a family with multiple members affected with Tourette syndrome. In addition, a patient with a deletion of 18q21.3-qter and Tourette syndrome has also been reported. These cases suggest that a gene involved in the etiology of Tourette syndrome maps in 18q, specifically at the site of the translocation breakpoint. A blood sample has been obtained from one of the individuals inheriting the balanced translocation and the location of the translocation with respect to numerous chromosome 18 DNA markers has been determined. Two yeast artificial chromosomes have been identified by fluorescent in situ hybridization that span the translocation breakpoint. This proposal describes the experimental approach for identifying genes that map at the translocation breakpoint. First, a cosmid clone will be identified that maps at the translocation breakpoint. This cosmid clone will then be used to identify additional clones of both chromosome 7 and chromosome 18 origin that will be used to identify genes that map at the breakpoint region. The genes will be characterized to determine whether their expression could be altered by the presence of the translocation. Their tissue-specific expression pattern will be characterized to determine their potentials as a candidate gene for Tourette syndrome.